Hidden Mastocytosis in AML with t(8;21)
Ryan C Johnson, Natasha M Savage, Tsoyu Chiang, Jason R Gotlib, Daniel A Arber, Tracy I George. Stanford University, Stanford, CA
Background: An increased incidence of mastocytosis has been reported in association with acute myeloid leukemia (AML) with t(8;21)(q22;q22). We retrospectively analyzed a large series of patients with t(8;21) AML to assess the frequency of mastocytosis via morphologic, immunohistochemical, clinical, and KIT mutational analysis.
Design: 41 patients (age range 5-68, including 7 pediatric cases) with t(8;21) AML were identified from our institutional database from 1990-2011 with diagnostic bone marrow specimens. Mast cell morphology was assessed via Wright-Giemsa stained aspirate smears, and core biopsies were stained with H&E. Immunohistochemical staining was performed via an automated platform (Ventana Benchmark, Tucson, AZ) and antibodies to tryptase and CD25 were performed on bone marrow core biopsy samples. Polymerase chain reaction (PCR) amplification and sequencing of KIT was performed on bone marrow aspirates with probes directed at exon 17 of the KIT gene and directly sequenced.
Results: All cases showed H&E stained core biopsies compatible with acute leukemia without overt histology suggestive of mastocytosis. After immunohistochemistry, morphology, and KIT mutational analysis, 4/41 cases (including 1/7 pediatric cases) met WHO criteria for systemic mastocytosis (9.7%), 6/41 cases showed mast cell hyperplasia (14.6%), and one case met criteria for myelomastocytic leukemia. Additionally, four other cases (9.7%) demonstrated atypical findings including CD25-positive clustered mast cells or KIT exon 17 point mutations (e.g., D816V, D816K), but did not meet sufficient criteria for systemic mastocytosis or myelomastocytic leukemia.
Conclusions: This is one of the largest series to date assessing for mast cell disease in patients with t(8;21) AML. Using tryptase immunohistochemistry we identified a significant proportion of patients (11/41) who demonstrated increased interstitial or clustered mast cells on the core biopsy not seen on initial pathology diagnosis based on standard review of bone marrow aspirates, biopsy, and flow cytometry--of these, four met WHO criteria for systemic mastocytosis after morphologic assessment, CD25 immunohistochemistry and KIT mutation testing. Four additional cases demonstrated atypical/aberrant mast cell findings or the presence of exon 17 KIT mutations but did not meet criteria for mastocytosis, the significance of which is unclear. We recommend routinely assessing for the presence of systemic mastocytosis in patients with t(8;21) AML via immunohistochemical and/or KIT mutational analysis.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 244, Monday Morning